Monitoring of genetic diversity in the Japanese Black cattle population by the use of pedigree information

The gene pool of the Japanese Black cattle has been completely closed to foreign breeds during the last 100 years. Genetic diversity of the Japanese Black cattle from 1960 to 2000 was monitored with three estimates of effective number of ancestors. Founder genome equivalent (N_ge) accounts for all the causes of reduction of diversity. Effective number of founders (N_ef) and non‐founders (N_enf) explain reduced diversity because of unequal genetic contributions of founders and random genetic drift in non‐founders, respectively. Further examination using gene dropping simulation was conducted to obtain information on survival of founder alleles. Unique founder alleles were dropped down along the actual pedigree with Monte Carlo procedure following Mendelian segregation rules, and generated genotypes of all the current live animals (612 959 heads). Pedigree records consisted of 2 075 188 animals was used for these analysis. The estimates of three effective numbers (N_ef, N_ge, and N_enf) decreased from 418.6 to 50.3, 86.6 to 7.3, and 109.2 to 8.5, respectively, during the period 1960–2000. The increasing differences between two kinds of genetic diversity indices derived from N_ge and N_ef showed that large part of the reduced diversity from 1980 was attributed to genetic drift caused by the intensive use of particular limited number of sires. In gene dropping analysis, probabilities of extinction of founder alleles were derived from their distributions of frequency in the current animals. Several founders showed low probabilities of allele extinction, irrespective of their relatively low genetic contributions. This suggests that these founders have lineages through which their alleles are surely transmitted to the current breed. The use of these founders as a strategy for recovering the genetic diversity was discussed.     

Variance component estimation on the frequency of pathologic changes in the navicular bones of Hanoverian Warmblood horses

The results of a standardized radiological examination of 3748 young Hanoverian Warmblood horses selected for sale at auction as riding horses were used to quantify the influence of systematic effects on and to estimate genetic parameters for the prevalence of pathologic changes in the navicular bones. Radiographic findings in the navicular bones of the front limbs were analyzed as all‐or‐none traits. The pathologic changes were mostly classified as slight [PCN(I); 14.9%], less often as moderate [PCN(II); 5.3%] or severe [PCN(III); 1.8%]. Date and year of auction had a significant influence on the prevalence of documented radiographic findings. The prevalence of PCN(I) was further significantly dependent on the examiner, the type and the quality of auction. PCN(II) was significantly more prevalent in male than in female horses. The age, the anticipated suitability and the region of origin of the horses did not have any significant influence on the prevalence of pathologic changes in navicular bones. A higher percentage of genes of the Hanoverian and the Holstein Warmblood horse increased the probability of PCN(I) classification. A significant influence of the sire was found for PCN(I) and PCN(II), and of the male founder for PCN(II) and PCN(III). The female founder was significant only for PCN(II). In general, radiographic findings of any severity in front left and right navicular bones were significantly correlated with each other. Restricted maximum likelihood (REML) was used for the estimation of genetic parameters. The analyses were performed multivariately in linear animal and sire models including height at withers as a separate trait. Heritability estimates for the prevalence of PCN(I), PCN(II) and PCN(III) of horses of both sexes ranged between h² = 0.09 and 0.21. When distinguishing between findings in males and females, somewhat implausible estimates were obtained for PCN(II) in females, which might have been caused by their low prevalence. The additive genetic correlations between the investigated traits indicated that radiographic findings consistent with navicular syndrome have a uniform genetic pattern in males and in females, and irrespective of their severity. However, their genetic correlation to height at withers was found to be inconsistent and, therefore, not to be utilizable for selection.     

FC-17 Cutaneous papillomatosis and carcinomatosis in the highly endangered Western Barred Bandicoot

Newcastle disease virus (NDV) has antineoplastic and immunostimulatory properties, and it is currently being clinically tested in anticancer therapy. In order to analyse the immunostimulatory effects of NDV on bovine papillomatosis, we inoculated 14 cows subcutaneously with an attenuated vaccine containing the LaSota strain of NDV (LS-NDV). Four cows with papillomatosis served as controls. Serum samples were collected from each animal 1 h preinoculation and 7 and 21 days postinoculation. In inoculated cows on days 7 and 21, the mean antibody titres were log₂ 2.43 ± 0.92 and 5.57 ± 0.72, respectively, by haemagglutination inhibition, and the mean levels of TNFα were 5.80 ± 4.19 and 5.39 ± 2.66 ng/mL, respectively, by WEHI-164 cytotoxicity assay. Significant differences between inoculated and control animals were evident for antibody titres on day 21 and clinical scores on day 60. A correlation was evident between the TNFα activities and clinical scores on day 21. The clinical observations at day 60 showed that the papillomas in five cows had completely resolved (36%), one animal had no alterations on clinical appearance of the tumour (7%), and papillomas in eight cows had regressed (57%). In conclusion, these results demonstrated that inoculation of LS-NDV vaccine stimulates an antibody response and a limited increase in TNFα activity and may enhance clinical recovery in bovine papillomatosis.
Funding: Scientific Research Council of Akdeniz University.     

Results from the treatment of advanced stage squamous cell carcinoma of the nasal planum in cats, using a combination of intralesional carboplatin and superficial radiotherapy: a pilot study

Six cats with an advanced stage squamous cell carcinoma (SCC) of the nasal planum were treated with a combination of superficial radiotherapy and intralesional carboplatin therapy. This multimodality protocol was well tolerated by the majority of cats and resulted in complete responses in all cats (100%). Median follow‐up for all cats is 268 days, and the median time‐to‐recurrence, time‐to‐progression and overall survival have not yet been reached. Our study, although limited in number of animals and with a relatively short median follow‐up compared to other studies for this disease, suggests that a combination of radiotherapy and intralesional carboplatin is a useful treatment option for an advanced stage SCC of the nasal planum in cats and warrants further application of the multimodality approach presented here.     

Monitoring response to aminobisphosphonate therapy in canine osteosarcoma using dual energy x‐ray absorptiometry (dexa)

Introduction: Palliative therapy is essential to improve the quality of life of dogs with osteosarcoma (OSA), when definitive therapy is not considered a valid option. Bisphosphonates, a novel class of antiosteoclastic drugs, are widely used in humans for several painful osteolytic conditions. Dual energy x‐ray absorptiometry (DEXA) is recognized as a reliable tool to measure bone mineral density (BMD), and to monitor treatment response to bisphosphonates in humans. A prospective evaluation of pamidronate, an injectable aminobisphosphonate, is ongoing in dogs with appendicular OSA. The potential value of DEXA for objective evaluation of BMD variations with palliative therapies is concurrently being assessed. Materials and Methods: Dogs with naturally occurring appendicular OSA treated with pamidronate constitute the patient population. A DEXA scan (QDR‐4500 W, Hologic, Bedford, MA) is performed on day 0 (baseline) and on every treatment day with pamidronate thereafter (every 28 days). For each dog, a whole body scan is performed, followed by a scan of the tumor, and contralateral normal bone. Three regions of interest are subsequently analyzed for BMD changes in tumor and normal bone. Statistical analysis was performed using Student t‐test and paired t‐tests, with significance being set at p < 0.05. Results: Nineteen dogs have been enrolled to date. Seven responders and 6 non‐responders have suitable data for analysis. A significant difference is observed (p = 0.04) between tumor BMD variations of responders and non‐responders at day 28 (mean variations +18.0% and ?4.6% respectively). The changes at day 28 are significant only in the responders (p = 0.038 vs p = 0.05 in non‐responders). When BMD of tumor and normal bone at day 84 is compared to day 0 in six responders, only tumor had a significant increase (p = 0.017 vs p = 0.279, respectively). Conclusions: Objective measurements of response to therapy are essential in pain palliation studies. Increased tumor bone BMD, as obtained by DEXA analysis, may correlate with subjective clinical improvement in pamidronate‐treated dogs with appendicular OSA.     

Noninvasive monitoring of doxorubicin cardiotoxicity: a pilot study of two dogs

The cardiotoxicity of anthracycline anticancer agents, most notably doxorubicin, limits their use in treating a wide variety of cancers. Currently available methods for assessment of anthracycline‐induced cardiotoxicity (AIC) often lack specificity and sensitivity. The purpose of this pilot investigation was to determine noninvasive diagnostic methods that are predictive for AIC. Two mongrel dogs were anesthetized for injection of doxorubicin (22.5 mg) directly into the left coronary artery. Doxorubicin injection was repeated 2 weeks later. Dogs were followed for 12 weeks or until heart failure was documented. Dogs were monitored before and at serial time points after doxorubicin using echocardiography and signal‐averaged electrocardiography as well as ambulatory ECG monitoring. Blood was also collected for measurement of cardiac troponin I and T concentrations. Doxorubicin was readministered at 6 and 12 weeks after the second injection, as interim data analysis did not reveal adequate evidence of cardiomyopathy. Dog‐1 appeared to be more sensitive than Dog‐2 to AIC based upon gradual changes in variables of cardiac function and earlier time to failure (113 days). In contrast, Dog‐2 had inconsistent changes in cardiac function and a longer time to failure (139 days). Dog‐1 also had greater peak plasma cardiac troponin I levels (17.96 ng/ml) as compared to peak levels in Dog‐2 (4.08 ng/ml). In addition, Dog‐1 had increased ventricular extrasystolic contractions (VE)(0/day at baseline, 443/day one week prior to death), whereas dog‐2 showed very few VE's throughout. Spectral analysis of ECG data also revealed a significant decrease over time in total spectral power in Dog‐1 from 37,148 at baseline to 603 msec²/Hz one week prior to death, indicating decreased parasympathetic tone. Endomyocardial biopsies revealed minor changes despite significant clinical abnormalities. These data indicate differences in susceptibility to AIC between Dog‐1 and Dog‐2, and suggest a role for these noninvasive measures in monitoring the heart during chemotherapy.